Efficacy and safety of exogenous ketone bodies for preventive treatment of migraine: A study protocol for a single-centred, randomised, placebo-controlled, double-blind crossover trial

Abstract Background Currently available prophylactic migraine treatment options are limited and are associated with many, often intolerable, side-effects. Various lines of research suggest that abnormalities in energy metabolism are likely to be part of migraine pathophysiology. Previously, a ketogenic diet (KD) has been reported to lead to a drastic reduction in migraine frequency. An alternative method to a strict KD is inducing a mild nutritional ketosis (0.4–2 mmol/l) with exogenous ketogenic substances. The aim of this randomised, placebo-controlled, double-blind, crossover, single-centre trial is to demonstrate safety and superiority of beta-hydroxybutyrate (βHB) in mineral salt form over placebo in migraine prevention. Methods/design Forty-five episodic migraineurs (5–14 migraine days/months), with or without aura, aged between 18 and 65 years, will be recruited at headache clinics in Switzerland, Germany and Austria and via Internet announcements. After a 4-week baseline period, patients will be randomly allocated to one of the two trial arms and receive either the βHB mineral salt or placebo for 12 weeks. This will be followed by a 4-week wash-out period, a subsequent second baseline period and, finally, another 12-week intervention with the alternative treatment. Co-medication with triptans (10 days per months) or analgesics (14 days per months) is permitted. The primary outcome is the mean change from baseline in the number of migraine days (meeting International Classification of Headache Disorders version 3 criteria) during the last 4 weeks of intervention compared to placebo. Secondary endpoints include mean changes in headache days of any severity, acute migraine medication use, migraine intensity and migraine and headache-related disability. Exploratory outcomes are (in addition to routine laboratory analysis) genetic profiling and expression analysis, oxidative and nitrosative stress, as well as serum cytokine analysis, and blood βHB and glucose analysis (pharmacokinetics). Discussion A crossover design was chosen as it greatly improves statistical power and participation rates, without increasing costs. To our knowledge this is the first RCT using βHB salts worldwide. If proven effective and safe, βHB might not only offer a new prophylactic treatment option for migraine patients, but might additionally pave the way for clinical trials assessing its use in related diseases. Trial registration ClinicalTrials.gov, NCT03132233. Registered on 27 April 2017. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Elena Gross [verfasserIn] Niveditha Putananickal [verfasserIn] Anna-Lena Orsini [verfasserIn] Simone Schmidt [verfasserIn] Deborah R. Vogt [verfasserIn] Sven Cichon [verfasserIn] Peter Sandor [verfasserIn] Dirk Fischer [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	Migraine Migraine prevention Exogenous ketone bodies Beta-hydroxybutyrate 3-Hydroxybutyrate Ketosis

Übergeordnetes Werk:	In: Trials - BMC, 2006, 20(2019), 1, Seite 18
Übergeordnetes Werk:	volume:20 ; year:2019 ; number:1 ; pages:18

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s13063-018-3120-7

Katalog-ID:	DOAJ064241076

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520			\|a Abstract Background Currently available prophylactic migraine treatment options are limited and are associated with many, often intolerable, side-effects. Various lines of research suggest that abnormalities in energy metabolism are likely to be part of migraine pathophysiology. Previously, a ketogenic diet (KD) has been reported to lead to a drastic reduction in migraine frequency. An alternative method to a strict KD is inducing a mild nutritional ketosis (0.4–2 mmol/l) with exogenous ketogenic substances. The aim of this randomised, placebo-controlled, double-blind, crossover, single-centre trial is to demonstrate safety and superiority of beta-hydroxybutyrate (βHB) in mineral salt form over placebo in migraine prevention. Methods/design Forty-five episodic migraineurs (5–14 migraine days/months), with or without aura, aged between 18 and 65 years, will be recruited at headache clinics in Switzerland, Germany and Austria and via Internet announcements. After a 4-week baseline period, patients will be randomly allocated to one of the two trial arms and receive either the βHB mineral salt or placebo for 12 weeks. This will be followed by a 4-week wash-out period, a subsequent second baseline period and, finally, another 12-week intervention with the alternative treatment. Co-medication with triptans (10 days per months) or analgesics (14 days per months) is permitted. The primary outcome is the mean change from baseline in the number of migraine days (meeting International Classification of Headache Disorders version 3 criteria) during the last 4 weeks of intervention compared to placebo. Secondary endpoints include mean changes in headache days of any severity, acute migraine medication use, migraine intensity and migraine and headache-related disability. Exploratory outcomes are (in addition to routine laboratory analysis) genetic profiling and expression analysis, oxidative and nitrosative stress, as well as serum cytokine analysis, and blood βHB and glucose analysis (pharmacokinetics). Discussion A crossover design was chosen as it greatly improves statistical power and participation rates, without increasing costs. To our knowledge this is the first RCT using βHB salts worldwide. If proven effective and safe, βHB might not only offer a new prophylactic treatment option for migraine patients, but might additionally pave the way for clinical trials assessing its use in related diseases. Trial registration ClinicalTrials.gov, NCT03132233. Registered on 27 April 2017.
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allfields	10.1186/s13063-018-3120-7 doi (DE-627)DOAJ064241076 (DE-599)DOAJd62e04c5311546acb34188e431207d42 DE-627 ger DE-627 rakwb eng R5-920 Elena Gross verfasserin aut Efficacy and safety of exogenous ketone bodies for preventive treatment of migraine: A study protocol for a single-centred, randomised, placebo-controlled, double-blind crossover trial 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Currently available prophylactic migraine treatment options are limited and are associated with many, often intolerable, side-effects. Various lines of research suggest that abnormalities in energy metabolism are likely to be part of migraine pathophysiology. Previously, a ketogenic diet (KD) has been reported to lead to a drastic reduction in migraine frequency. An alternative method to a strict KD is inducing a mild nutritional ketosis (0.4–2 mmol/l) with exogenous ketogenic substances. The aim of this randomised, placebo-controlled, double-blind, crossover, single-centre trial is to demonstrate safety and superiority of beta-hydroxybutyrate (βHB) in mineral salt form over placebo in migraine prevention. Methods/design Forty-five episodic migraineurs (5–14 migraine days/months), with or without aura, aged between 18 and 65 years, will be recruited at headache clinics in Switzerland, Germany and Austria and via Internet announcements. After a 4-week baseline period, patients will be randomly allocated to one of the two trial arms and receive either the βHB mineral salt or placebo for 12 weeks. This will be followed by a 4-week wash-out period, a subsequent second baseline period and, finally, another 12-week intervention with the alternative treatment. Co-medication with triptans (10 days per months) or analgesics (14 days per months) is permitted. The primary outcome is the mean change from baseline in the number of migraine days (meeting International Classification of Headache Disorders version 3 criteria) during the last 4 weeks of intervention compared to placebo. Secondary endpoints include mean changes in headache days of any severity, acute migraine medication use, migraine intensity and migraine and headache-related disability. Exploratory outcomes are (in addition to routine laboratory analysis) genetic profiling and expression analysis, oxidative and nitrosative stress, as well as serum cytokine analysis, and blood βHB and glucose analysis (pharmacokinetics). Discussion A crossover design was chosen as it greatly improves statistical power and participation rates, without increasing costs. To our knowledge this is the first RCT using βHB salts worldwide. If proven effective and safe, βHB might not only offer a new prophylactic treatment option for migraine patients, but might additionally pave the way for clinical trials assessing its use in related diseases. Trial registration ClinicalTrials.gov, NCT03132233. Registered on 27 April 2017. Migraine Migraine prevention Exogenous ketone bodies Beta-hydroxybutyrate 3-Hydroxybutyrate Ketosis Medicine (General) Niveditha Putananickal verfasserin aut Anna-Lena Orsini verfasserin aut Simone Schmidt verfasserin aut Deborah R. Vogt verfasserin aut Sven Cichon verfasserin aut Peter Sandor verfasserin aut Dirk Fischer verfasserin aut In Trials BMC, 2006 20(2019), 1, Seite 18 (DE-627)326173552 (DE-600)2040523-6 17456215 nnns volume:20 year:2019 number:1 pages:18 https://doi.org/10.1186/s13063-018-3120-7 kostenfrei https://doaj.org/article/d62e04c5311546acb34188e431207d42 kostenfrei http://link.springer.com/article/10.1186/s13063-018-3120-7 kostenfrei https://doaj.org/toc/1745-6215 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2019 1 18
spelling	10.1186/s13063-018-3120-7 doi (DE-627)DOAJ064241076 (DE-599)DOAJd62e04c5311546acb34188e431207d42 DE-627 ger DE-627 rakwb eng R5-920 Elena Gross verfasserin aut Efficacy and safety of exogenous ketone bodies for preventive treatment of migraine: A study protocol for a single-centred, randomised, placebo-controlled, double-blind crossover trial 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Currently available prophylactic migraine treatment options are limited and are associated with many, often intolerable, side-effects. Various lines of research suggest that abnormalities in energy metabolism are likely to be part of migraine pathophysiology. Previously, a ketogenic diet (KD) has been reported to lead to a drastic reduction in migraine frequency. An alternative method to a strict KD is inducing a mild nutritional ketosis (0.4–2 mmol/l) with exogenous ketogenic substances. The aim of this randomised, placebo-controlled, double-blind, crossover, single-centre trial is to demonstrate safety and superiority of beta-hydroxybutyrate (βHB) in mineral salt form over placebo in migraine prevention. Methods/design Forty-five episodic migraineurs (5–14 migraine days/months), with or without aura, aged between 18 and 65 years, will be recruited at headache clinics in Switzerland, Germany and Austria and via Internet announcements. After a 4-week baseline period, patients will be randomly allocated to one of the two trial arms and receive either the βHB mineral salt or placebo for 12 weeks. This will be followed by a 4-week wash-out period, a subsequent second baseline period and, finally, another 12-week intervention with the alternative treatment. Co-medication with triptans (10 days per months) or analgesics (14 days per months) is permitted. The primary outcome is the mean change from baseline in the number of migraine days (meeting International Classification of Headache Disorders version 3 criteria) during the last 4 weeks of intervention compared to placebo. Secondary endpoints include mean changes in headache days of any severity, acute migraine medication use, migraine intensity and migraine and headache-related disability. Exploratory outcomes are (in addition to routine laboratory analysis) genetic profiling and expression analysis, oxidative and nitrosative stress, as well as serum cytokine analysis, and blood βHB and glucose analysis (pharmacokinetics). Discussion A crossover design was chosen as it greatly improves statistical power and participation rates, without increasing costs. To our knowledge this is the first RCT using βHB salts worldwide. If proven effective and safe, βHB might not only offer a new prophylactic treatment option for migraine patients, but might additionally pave the way for clinical trials assessing its use in related diseases. Trial registration ClinicalTrials.gov, NCT03132233. Registered on 27 April 2017. Migraine Migraine prevention Exogenous ketone bodies Beta-hydroxybutyrate 3-Hydroxybutyrate Ketosis Medicine (General) Niveditha Putananickal verfasserin aut Anna-Lena Orsini verfasserin aut Simone Schmidt verfasserin aut Deborah R. Vogt verfasserin aut Sven Cichon verfasserin aut Peter Sandor verfasserin aut Dirk Fischer verfasserin aut In Trials BMC, 2006 20(2019), 1, Seite 18 (DE-627)326173552 (DE-600)2040523-6 17456215 nnns volume:20 year:2019 number:1 pages:18 https://doi.org/10.1186/s13063-018-3120-7 kostenfrei https://doaj.org/article/d62e04c5311546acb34188e431207d42 kostenfrei http://link.springer.com/article/10.1186/s13063-018-3120-7 kostenfrei https://doaj.org/toc/1745-6215 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2019 1 18
allfields_unstemmed	10.1186/s13063-018-3120-7 doi (DE-627)DOAJ064241076 (DE-599)DOAJd62e04c5311546acb34188e431207d42 DE-627 ger DE-627 rakwb eng R5-920 Elena Gross verfasserin aut Efficacy and safety of exogenous ketone bodies for preventive treatment of migraine: A study protocol for a single-centred, randomised, placebo-controlled, double-blind crossover trial 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Currently available prophylactic migraine treatment options are limited and are associated with many, often intolerable, side-effects. Various lines of research suggest that abnormalities in energy metabolism are likely to be part of migraine pathophysiology. Previously, a ketogenic diet (KD) has been reported to lead to a drastic reduction in migraine frequency. An alternative method to a strict KD is inducing a mild nutritional ketosis (0.4–2 mmol/l) with exogenous ketogenic substances. The aim of this randomised, placebo-controlled, double-blind, crossover, single-centre trial is to demonstrate safety and superiority of beta-hydroxybutyrate (βHB) in mineral salt form over placebo in migraine prevention. Methods/design Forty-five episodic migraineurs (5–14 migraine days/months), with or without aura, aged between 18 and 65 years, will be recruited at headache clinics in Switzerland, Germany and Austria and via Internet announcements. After a 4-week baseline period, patients will be randomly allocated to one of the two trial arms and receive either the βHB mineral salt or placebo for 12 weeks. This will be followed by a 4-week wash-out period, a subsequent second baseline period and, finally, another 12-week intervention with the alternative treatment. Co-medication with triptans (10 days per months) or analgesics (14 days per months) is permitted. The primary outcome is the mean change from baseline in the number of migraine days (meeting International Classification of Headache Disorders version 3 criteria) during the last 4 weeks of intervention compared to placebo. Secondary endpoints include mean changes in headache days of any severity, acute migraine medication use, migraine intensity and migraine and headache-related disability. Exploratory outcomes are (in addition to routine laboratory analysis) genetic profiling and expression analysis, oxidative and nitrosative stress, as well as serum cytokine analysis, and blood βHB and glucose analysis (pharmacokinetics). Discussion A crossover design was chosen as it greatly improves statistical power and participation rates, without increasing costs. To our knowledge this is the first RCT using βHB salts worldwide. If proven effective and safe, βHB might not only offer a new prophylactic treatment option for migraine patients, but might additionally pave the way for clinical trials assessing its use in related diseases. Trial registration ClinicalTrials.gov, NCT03132233. Registered on 27 April 2017. Migraine Migraine prevention Exogenous ketone bodies Beta-hydroxybutyrate 3-Hydroxybutyrate Ketosis Medicine (General) Niveditha Putananickal verfasserin aut Anna-Lena Orsini verfasserin aut Simone Schmidt verfasserin aut Deborah R. Vogt verfasserin aut Sven Cichon verfasserin aut Peter Sandor verfasserin aut Dirk Fischer verfasserin aut In Trials BMC, 2006 20(2019), 1, Seite 18 (DE-627)326173552 (DE-600)2040523-6 17456215 nnns volume:20 year:2019 number:1 pages:18 https://doi.org/10.1186/s13063-018-3120-7 kostenfrei https://doaj.org/article/d62e04c5311546acb34188e431207d42 kostenfrei http://link.springer.com/article/10.1186/s13063-018-3120-7 kostenfrei https://doaj.org/toc/1745-6215 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2019 1 18
allfieldsGer	10.1186/s13063-018-3120-7 doi (DE-627)DOAJ064241076 (DE-599)DOAJd62e04c5311546acb34188e431207d42 DE-627 ger DE-627 rakwb eng R5-920 Elena Gross verfasserin aut Efficacy and safety of exogenous ketone bodies for preventive treatment of migraine: A study protocol for a single-centred, randomised, placebo-controlled, double-blind crossover trial 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Currently available prophylactic migraine treatment options are limited and are associated with many, often intolerable, side-effects. Various lines of research suggest that abnormalities in energy metabolism are likely to be part of migraine pathophysiology. Previously, a ketogenic diet (KD) has been reported to lead to a drastic reduction in migraine frequency. An alternative method to a strict KD is inducing a mild nutritional ketosis (0.4–2 mmol/l) with exogenous ketogenic substances. The aim of this randomised, placebo-controlled, double-blind, crossover, single-centre trial is to demonstrate safety and superiority of beta-hydroxybutyrate (βHB) in mineral salt form over placebo in migraine prevention. Methods/design Forty-five episodic migraineurs (5–14 migraine days/months), with or without aura, aged between 18 and 65 years, will be recruited at headache clinics in Switzerland, Germany and Austria and via Internet announcements. After a 4-week baseline period, patients will be randomly allocated to one of the two trial arms and receive either the βHB mineral salt or placebo for 12 weeks. This will be followed by a 4-week wash-out period, a subsequent second baseline period and, finally, another 12-week intervention with the alternative treatment. Co-medication with triptans (10 days per months) or analgesics (14 days per months) is permitted. The primary outcome is the mean change from baseline in the number of migraine days (meeting International Classification of Headache Disorders version 3 criteria) during the last 4 weeks of intervention compared to placebo. Secondary endpoints include mean changes in headache days of any severity, acute migraine medication use, migraine intensity and migraine and headache-related disability. Exploratory outcomes are (in addition to routine laboratory analysis) genetic profiling and expression analysis, oxidative and nitrosative stress, as well as serum cytokine analysis, and blood βHB and glucose analysis (pharmacokinetics). Discussion A crossover design was chosen as it greatly improves statistical power and participation rates, without increasing costs. To our knowledge this is the first RCT using βHB salts worldwide. If proven effective and safe, βHB might not only offer a new prophylactic treatment option for migraine patients, but might additionally pave the way for clinical trials assessing its use in related diseases. Trial registration ClinicalTrials.gov, NCT03132233. Registered on 27 April 2017. Migraine Migraine prevention Exogenous ketone bodies Beta-hydroxybutyrate 3-Hydroxybutyrate Ketosis Medicine (General) Niveditha Putananickal verfasserin aut Anna-Lena Orsini verfasserin aut Simone Schmidt verfasserin aut Deborah R. Vogt verfasserin aut Sven Cichon verfasserin aut Peter Sandor verfasserin aut Dirk Fischer verfasserin aut In Trials BMC, 2006 20(2019), 1, Seite 18 (DE-627)326173552 (DE-600)2040523-6 17456215 nnns volume:20 year:2019 number:1 pages:18 https://doi.org/10.1186/s13063-018-3120-7 kostenfrei https://doaj.org/article/d62e04c5311546acb34188e431207d42 kostenfrei http://link.springer.com/article/10.1186/s13063-018-3120-7 kostenfrei https://doaj.org/toc/1745-6215 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2019 1 18
allfieldsSound	10.1186/s13063-018-3120-7 doi (DE-627)DOAJ064241076 (DE-599)DOAJd62e04c5311546acb34188e431207d42 DE-627 ger DE-627 rakwb eng R5-920 Elena Gross verfasserin aut Efficacy and safety of exogenous ketone bodies for preventive treatment of migraine: A study protocol for a single-centred, randomised, placebo-controlled, double-blind crossover trial 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Currently available prophylactic migraine treatment options are limited and are associated with many, often intolerable, side-effects. Various lines of research suggest that abnormalities in energy metabolism are likely to be part of migraine pathophysiology. Previously, a ketogenic diet (KD) has been reported to lead to a drastic reduction in migraine frequency. An alternative method to a strict KD is inducing a mild nutritional ketosis (0.4–2 mmol/l) with exogenous ketogenic substances. The aim of this randomised, placebo-controlled, double-blind, crossover, single-centre trial is to demonstrate safety and superiority of beta-hydroxybutyrate (βHB) in mineral salt form over placebo in migraine prevention. Methods/design Forty-five episodic migraineurs (5–14 migraine days/months), with or without aura, aged between 18 and 65 years, will be recruited at headache clinics in Switzerland, Germany and Austria and via Internet announcements. After a 4-week baseline period, patients will be randomly allocated to one of the two trial arms and receive either the βHB mineral salt or placebo for 12 weeks. This will be followed by a 4-week wash-out period, a subsequent second baseline period and, finally, another 12-week intervention with the alternative treatment. Co-medication with triptans (10 days per months) or analgesics (14 days per months) is permitted. The primary outcome is the mean change from baseline in the number of migraine days (meeting International Classification of Headache Disorders version 3 criteria) during the last 4 weeks of intervention compared to placebo. Secondary endpoints include mean changes in headache days of any severity, acute migraine medication use, migraine intensity and migraine and headache-related disability. Exploratory outcomes are (in addition to routine laboratory analysis) genetic profiling and expression analysis, oxidative and nitrosative stress, as well as serum cytokine analysis, and blood βHB and glucose analysis (pharmacokinetics). Discussion A crossover design was chosen as it greatly improves statistical power and participation rates, without increasing costs. To our knowledge this is the first RCT using βHB salts worldwide. If proven effective and safe, βHB might not only offer a new prophylactic treatment option for migraine patients, but might additionally pave the way for clinical trials assessing its use in related diseases. Trial registration ClinicalTrials.gov, NCT03132233. Registered on 27 April 2017. Migraine Migraine prevention Exogenous ketone bodies Beta-hydroxybutyrate 3-Hydroxybutyrate Ketosis Medicine (General) Niveditha Putananickal verfasserin aut Anna-Lena Orsini verfasserin aut Simone Schmidt verfasserin aut Deborah R. Vogt verfasserin aut Sven Cichon verfasserin aut Peter Sandor verfasserin aut Dirk Fischer verfasserin aut In Trials BMC, 2006 20(2019), 1, Seite 18 (DE-627)326173552 (DE-600)2040523-6 17456215 nnns volume:20 year:2019 number:1 pages:18 https://doi.org/10.1186/s13063-018-3120-7 kostenfrei https://doaj.org/article/d62e04c5311546acb34188e431207d42 kostenfrei http://link.springer.com/article/10.1186/s13063-018-3120-7 kostenfrei https://doaj.org/toc/1745-6215 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2019 1 18
language	English
source	In Trials 20(2019), 1, Seite 18 volume:20 year:2019 number:1 pages:18
sourceStr	In Trials 20(2019), 1, Seite 18 volume:20 year:2019 number:1 pages:18
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Migraine Migraine prevention Exogenous ketone bodies Beta-hydroxybutyrate 3-Hydroxybutyrate Ketosis Medicine (General)
isfreeaccess_bool	true
container_title	Trials
authorswithroles_txt_mv	Elena Gross @@aut@@ Niveditha Putananickal @@aut@@ Anna-Lena Orsini @@aut@@ Simone Schmidt @@aut@@ Deborah R. Vogt @@aut@@ Sven Cichon @@aut@@ Peter Sandor @@aut@@ Dirk Fischer @@aut@@
publishDateDaySort_date	2019-01-01T00:00:00Z
hierarchy_top_id	326173552
id	DOAJ064241076
language_de	englisch
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Various lines of research suggest that abnormalities in energy metabolism are likely to be part of migraine pathophysiology. Previously, a ketogenic diet (KD) has been reported to lead to a drastic reduction in migraine frequency. An alternative method to a strict KD is inducing a mild nutritional ketosis (0.4–2 mmol/l) with exogenous ketogenic substances. The aim of this randomised, placebo-controlled, double-blind, crossover, single-centre trial is to demonstrate safety and superiority of beta-hydroxybutyrate (βHB) in mineral salt form over placebo in migraine prevention. Methods/design Forty-five episodic migraineurs (5–14 migraine days/months), with or without aura, aged between 18 and 65 years, will be recruited at headache clinics in Switzerland, Germany and Austria and via Internet announcements. After a 4-week baseline period, patients will be randomly allocated to one of the two trial arms and receive either the βHB mineral salt or placebo for 12 weeks. This will be followed by a 4-week wash-out period, a subsequent second baseline period and, finally, another 12-week intervention with the alternative treatment. Co-medication with triptans (10 days per months) or analgesics (14 days per months) is permitted. The primary outcome is the mean change from baseline in the number of migraine days (meeting International Classification of Headache Disorders version 3 criteria) during the last 4 weeks of intervention compared to placebo. Secondary endpoints include mean changes in headache days of any severity, acute migraine medication use, migraine intensity and migraine and headache-related disability. Exploratory outcomes are (in addition to routine laboratory analysis) genetic profiling and expression analysis, oxidative and nitrosative stress, as well as serum cytokine analysis, and blood βHB and glucose analysis (pharmacokinetics). Discussion A crossover design was chosen as it greatly improves statistical power and participation rates, without increasing costs. To our knowledge this is the first RCT using βHB salts worldwide. If proven effective and safe, βHB might not only offer a new prophylactic treatment option for migraine patients, but might additionally pave the way for clinical trials assessing its use in related diseases. Trial registration ClinicalTrials.gov, NCT03132233. 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author	Elena Gross
spellingShingle	Elena Gross misc R5-920 misc Migraine misc Migraine prevention misc Exogenous ketone bodies misc Beta-hydroxybutyrate misc 3-Hydroxybutyrate misc Ketosis misc Medicine (General) Efficacy and safety of exogenous ketone bodies for preventive treatment of migraine: A study protocol for a single-centred, randomised, placebo-controlled, double-blind crossover trial
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topic_title	R5-920 Efficacy and safety of exogenous ketone bodies for preventive treatment of migraine: A study protocol for a single-centred, randomised, placebo-controlled, double-blind crossover trial Migraine Migraine prevention Exogenous ketone bodies Beta-hydroxybutyrate 3-Hydroxybutyrate Ketosis
topic	misc R5-920 misc Migraine misc Migraine prevention misc Exogenous ketone bodies misc Beta-hydroxybutyrate misc 3-Hydroxybutyrate misc Ketosis misc Medicine (General)
topic_unstemmed	misc R5-920 misc Migraine misc Migraine prevention misc Exogenous ketone bodies misc Beta-hydroxybutyrate misc 3-Hydroxybutyrate misc Ketosis misc Medicine (General)
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title	Efficacy and safety of exogenous ketone bodies for preventive treatment of migraine: A study protocol for a single-centred, randomised, placebo-controlled, double-blind crossover trial
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title_full	Efficacy and safety of exogenous ketone bodies for preventive treatment of migraine: A study protocol for a single-centred, randomised, placebo-controlled, double-blind crossover trial
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author_browse	Elena Gross Niveditha Putananickal Anna-Lena Orsini Simone Schmidt Deborah R. Vogt Sven Cichon Peter Sandor Dirk Fischer
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title_sort	efficacy and safety of exogenous ketone bodies for preventive treatment of migraine: a study protocol for a single-centred, randomised, placebo-controlled, double-blind crossover trial
callnumber	R5-920
title_auth	Efficacy and safety of exogenous ketone bodies for preventive treatment of migraine: A study protocol for a single-centred, randomised, placebo-controlled, double-blind crossover trial
abstract	Abstract Background Currently available prophylactic migraine treatment options are limited and are associated with many, often intolerable, side-effects. Various lines of research suggest that abnormalities in energy metabolism are likely to be part of migraine pathophysiology. Previously, a ketogenic diet (KD) has been reported to lead to a drastic reduction in migraine frequency. An alternative method to a strict KD is inducing a mild nutritional ketosis (0.4–2 mmol/l) with exogenous ketogenic substances. The aim of this randomised, placebo-controlled, double-blind, crossover, single-centre trial is to demonstrate safety and superiority of beta-hydroxybutyrate (βHB) in mineral salt form over placebo in migraine prevention. Methods/design Forty-five episodic migraineurs (5–14 migraine days/months), with or without aura, aged between 18 and 65 years, will be recruited at headache clinics in Switzerland, Germany and Austria and via Internet announcements. After a 4-week baseline period, patients will be randomly allocated to one of the two trial arms and receive either the βHB mineral salt or placebo for 12 weeks. This will be followed by a 4-week wash-out period, a subsequent second baseline period and, finally, another 12-week intervention with the alternative treatment. Co-medication with triptans (10 days per months) or analgesics (14 days per months) is permitted. The primary outcome is the mean change from baseline in the number of migraine days (meeting International Classification of Headache Disorders version 3 criteria) during the last 4 weeks of intervention compared to placebo. Secondary endpoints include mean changes in headache days of any severity, acute migraine medication use, migraine intensity and migraine and headache-related disability. Exploratory outcomes are (in addition to routine laboratory analysis) genetic profiling and expression analysis, oxidative and nitrosative stress, as well as serum cytokine analysis, and blood βHB and glucose analysis (pharmacokinetics). Discussion A crossover design was chosen as it greatly improves statistical power and participation rates, without increasing costs. To our knowledge this is the first RCT using βHB salts worldwide. If proven effective and safe, βHB might not only offer a new prophylactic treatment option for migraine patients, but might additionally pave the way for clinical trials assessing its use in related diseases. Trial registration ClinicalTrials.gov, NCT03132233. Registered on 27 April 2017.
abstractGer	Abstract Background Currently available prophylactic migraine treatment options are limited and are associated with many, often intolerable, side-effects. Various lines of research suggest that abnormalities in energy metabolism are likely to be part of migraine pathophysiology. Previously, a ketogenic diet (KD) has been reported to lead to a drastic reduction in migraine frequency. An alternative method to a strict KD is inducing a mild nutritional ketosis (0.4–2 mmol/l) with exogenous ketogenic substances. The aim of this randomised, placebo-controlled, double-blind, crossover, single-centre trial is to demonstrate safety and superiority of beta-hydroxybutyrate (βHB) in mineral salt form over placebo in migraine prevention. Methods/design Forty-five episodic migraineurs (5–14 migraine days/months), with or without aura, aged between 18 and 65 years, will be recruited at headache clinics in Switzerland, Germany and Austria and via Internet announcements. After a 4-week baseline period, patients will be randomly allocated to one of the two trial arms and receive either the βHB mineral salt or placebo for 12 weeks. This will be followed by a 4-week wash-out period, a subsequent second baseline period and, finally, another 12-week intervention with the alternative treatment. Co-medication with triptans (10 days per months) or analgesics (14 days per months) is permitted. The primary outcome is the mean change from baseline in the number of migraine days (meeting International Classification of Headache Disorders version 3 criteria) during the last 4 weeks of intervention compared to placebo. Secondary endpoints include mean changes in headache days of any severity, acute migraine medication use, migraine intensity and migraine and headache-related disability. Exploratory outcomes are (in addition to routine laboratory analysis) genetic profiling and expression analysis, oxidative and nitrosative stress, as well as serum cytokine analysis, and blood βHB and glucose analysis (pharmacokinetics). Discussion A crossover design was chosen as it greatly improves statistical power and participation rates, without increasing costs. To our knowledge this is the first RCT using βHB salts worldwide. If proven effective and safe, βHB might not only offer a new prophylactic treatment option for migraine patients, but might additionally pave the way for clinical trials assessing its use in related diseases. Trial registration ClinicalTrials.gov, NCT03132233. Registered on 27 April 2017.
abstract_unstemmed	Abstract Background Currently available prophylactic migraine treatment options are limited and are associated with many, often intolerable, side-effects. Various lines of research suggest that abnormalities in energy metabolism are likely to be part of migraine pathophysiology. Previously, a ketogenic diet (KD) has been reported to lead to a drastic reduction in migraine frequency. An alternative method to a strict KD is inducing a mild nutritional ketosis (0.4–2 mmol/l) with exogenous ketogenic substances. The aim of this randomised, placebo-controlled, double-blind, crossover, single-centre trial is to demonstrate safety and superiority of beta-hydroxybutyrate (βHB) in mineral salt form over placebo in migraine prevention. Methods/design Forty-five episodic migraineurs (5–14 migraine days/months), with or without aura, aged between 18 and 65 years, will be recruited at headache clinics in Switzerland, Germany and Austria and via Internet announcements. After a 4-week baseline period, patients will be randomly allocated to one of the two trial arms and receive either the βHB mineral salt or placebo for 12 weeks. This will be followed by a 4-week wash-out period, a subsequent second baseline period and, finally, another 12-week intervention with the alternative treatment. Co-medication with triptans (10 days per months) or analgesics (14 days per months) is permitted. The primary outcome is the mean change from baseline in the number of migraine days (meeting International Classification of Headache Disorders version 3 criteria) during the last 4 weeks of intervention compared to placebo. Secondary endpoints include mean changes in headache days of any severity, acute migraine medication use, migraine intensity and migraine and headache-related disability. Exploratory outcomes are (in addition to routine laboratory analysis) genetic profiling and expression analysis, oxidative and nitrosative stress, as well as serum cytokine analysis, and blood βHB and glucose analysis (pharmacokinetics). Discussion A crossover design was chosen as it greatly improves statistical power and participation rates, without increasing costs. To our knowledge this is the first RCT using βHB salts worldwide. If proven effective and safe, βHB might not only offer a new prophylactic treatment option for migraine patients, but might additionally pave the way for clinical trials assessing its use in related diseases. Trial registration ClinicalTrials.gov, NCT03132233. Registered on 27 April 2017.
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title_short	Efficacy and safety of exogenous ketone bodies for preventive treatment of migraine: A study protocol for a single-centred, randomised, placebo-controlled, double-blind crossover trial
url	https://doi.org/10.1186/s13063-018-3120-7 https://doaj.org/article/d62e04c5311546acb34188e431207d42 http://link.springer.com/article/10.1186/s13063-018-3120-7 https://doaj.org/toc/1745-6215
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Efficacy and safety of exogenous ketone bodies for preventive treatment of migraine: A study protocol for a single-centred, randomised, placebo-controlled, double-blind crossover trial

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